Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.

This tutorial is organized into three major sections—viruses, vaccines and the race for a Covid-19 vaccine. The goal is to provide enough background on viruses, history of vaccines, and the science of vaccinology founded on the principles of immunity. The hope is that this will enable us to understand the challenges, methods and prospects for developing a safe and effective vaccine against SARS-CoV-2. Many important viruses such as smallpox, HIV, HCV and SARS-CoV-2 which is responsible for causing the Coronavirus disease 2019 (Covid-19) are presented in detail, which is then followed by a description of different vaccine development methods and strategies. The tutorial then discusses different candidate SARS-CoV-2 vaccines and provides specific details of many of the prospective vaccines on the leader-board which are undergoing clinical trials. The tutorial concludes with a realistic projection for a safe and effective vaccine against SARS-CoV-2 based on the historical scientific record.

Rapid development and deployment of vaccines greatly reduced mortality and morbidity during the COVID-19 pandemic. The most widely used COVID-19 vaccines approved by national regulatory authorities require intramuscular administration. SARS-CoV-2 initially infects the upper respiratory tract where the infection can be eliminated with little or no symptoms by an effective immune response. Failure to eliminate SARS-CoV-2 in the upper respiratory tract results in lower respiratory tract infections that can lead to severe disease and death. Presently used intramuscularly administered COVID-19 vaccines are effective in reducing severe disease and mortality but are not entirely able to prevent asymptomatic and mild infections as well as person to person transmission of the virus. Individual and population differences also influence susceptibility to infection and the propensity to develop severe disease. This article provides a perspective on the nature and the mode of delivery COVID-19 vaccines that can optimize protective immunity in the upper respiratory tract to reduce infections and virus transmission as well as severe disease.

Introduction: The rapid emergence of COVID-19 as a global crisis has led to the approval of many vaccinations, which were unfortunately associated with high complication rates due to a lack of sufficient safety studies. Objectives: The following manuscript focuses on discussing the demyelinating disorders that were noticed after COVID vaccine administration. Methods: We conducted a retrospective study using anonymous medical records from the US vaccine adverse events reporting system, complications retrieved included Acute disseminated encephalomyelitis (ADEM), Guillain Barre syndrome (GBS), and Multiple sclerosis (MS), outcome parameters were age, sex and the dose after which this complication was observed. Patients younger than 18 years-old were excluded as some of the vaccines, namely Janssen (JNJ-78436735) is not yet approved below this age. Results: Our analysis showed that demyelinating disorders were more likely to occur in patients over the age of 50 compared to other age groups, regardless of the type of vaccination, except for MS and ADEM occurrences after the Jansen vaccine. In addition, demyelinating complications were more likely to occur after the first dose of vaccination. Conclusion: Further research and observation of demyelinating diseases in different vaccinations, as well as additional in vitro studies, are recommended to further explain the pathogenesis of demyelinating disorder occurrence.

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

Abstract: The emergence of the COVID-19 pandemic has led to the rapid and worldwide devel-opment and investigation of multiple vaccines. While most side effects of these vaccines are mild and transient, potentially severe adverse events may occur and involve the endocrine system. This narrative review aims to explore the current knowledge on potential endocrine adverse effects following COVID-19 vaccination, with thyroid disorders being the most common. Data about pi-tuitary, adrenal, diabetes, and gonadal events will also be reviewed. This review also provides a comprehensive understanding of the pathogenesis of endocrine disorders associated with SARS-CoV-2 vaccines. A PubMed/MEDLINE, Embase database (Elsevier), and Google Scholar research were performed. Case reports case series, original studies, and reviews written in English and published online up to 31 August 2023 were selected and reviewed. Data on endocrine adverse events of SARS-CoV-2 vaccines is accumulating. However, their causal relationship with COVID-19 vaccines is not strong enough to make a definite conclusion, and further studies are needed to clarify the pathogenesis mechanisms of endocrine disorders linked to COVID-19 vac-cines.

The global COVID-19 pandemic has affected all spheres of human life, resulting in millions of deaths and overwhelming medical facilities. Moreover, the world has witnessed great financial hardship because of job losses resulting in economic havoc. Many sections of society have contributed in different ways to slow the spread of the virus and protect public health. For example, medical scientists are praised for their efforts to develop COVID-19 vaccines. Clinical trials have shown that the COVID-19 vaccines are highly effective in preventing symptomatic COVID-19 infections. However, many people around the world have been hesitant to get vaccinated. Vaccine misconceptions have emerged and increased due to a combination of factors, including the availability of information on the Internet and the influence of celebrities and opinion leaders. In this context, we have analyzed ChatGPT responses to relevant queries on vaccine misconceptions. The positive responses and supportive opinions provided by the AI chatbot could be instrumental in shaping people’s perceptions of vaccines and in encouraging users to get vaccinated and reduce misconceptions.

Vaccination is one of the most effective methods for preventing morbidity and mortality from COVID-19. Vaccine hesitancy has led to a decrease in vaccine uptake; driven by misinformation, fear, and perceptions of vaccine safety. Whole inactivated vaccines have been used in one-fifth of the vaccine recipients in Africa, however there is limited real-world data on their safety. We evaluated the reported side effects and factors associated with reported side effects following vaccination with whole inactivated COVID-19 vaccines - BBiBP-CorV (Sinopharm) and CoronaVac (Sinovac). A quantitative survey evaluating attitudes and side effects from vaccination was administered to 1016 adults presenting at vaccination centers. Two follow-up telephone interviews were conducted to determine side effects after the first and second vaccination dose. Overall, the vaccine was well tolerated; 26.0% and 14.4% reported side effects after the first and second dose respectively. The most frequent local and systemic side effects were pain at the injection site and headaches respectively. Most symptoms were mild, and no participants re-quired hospitalization. Participants who perceived COVID-19 vaccines as safe or had a personal COVID-19 experience were significantly less likely to report side effects. Our findings provide data on the safety and tolerability of whole inactivated COVID-19 vaccines in an African population, providing the necessary data to create effective strategies to increase vaccination and support vaccination campaigns.

After the first weeks of vaccination against the SARS-CoV-2, several cases of acute thrombosis were reported. These news reports began to be shared frequently across social media platforms. The aim of this study was to conduct an analysis of Twitter data related to the overall discussion. Data was retrieved from 14th March to 14th April using the keyword ‘blood clots’. A dataset with n=266,677 tweets was retrieved, and a systematic random sample of 5% of tweets (n=13,334) were entered into NodeXL for further analysis. Social network analysis was used to analyse the data by drawing upon the Clauset-Newman-Moore algorithm. Influential users were identified by drawing upon the betweenness centrality metric. Text analysis was applied to identify the key hashtags and websites used at this time. More than half of the network was comprised of retweets and the largest groups within the network were broadcast clusters where a number of key users were retweeted. The most popular narratives were around highlighting the low risk of obtaining a blood clot from a vaccine and highlighting higher blood clot risks in medicines commonly consumed. A wide-variety of actors drove the discussion on Twitter ranging from writers, physicians, the general public academics, celebrities, and journalists. Twitter was used to highlight the low potential of obtaining a blood clot from a vaccine and encouraged vaccinations among the public.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress and fatality. At present, the global case fatality rate of COVID-19 laboratory confirmed cases is ~4.7% ranging from ~0.3-0.4% in Chile and Israel to ~10.8% in Italy. To address this global crisis, up-to-date information on the viral genomics and transcriptomics is crucial for understanding the origins and global dispersal of the virus, providing insight into viral pathogenicity, transmission and epidemiology, and enabling strategies for therapeutic interventions, drug discovery and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.

More than 600 Healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local, and systemic reactions were reported among physicians. This study aims to analyze the Adverse events (AEs) of COVID-19 vaccines with an emphasis on homologous and heterologous booster doses. An electronic survey was performed in Quito- Ecuador, directed to physicians who were vaccinated with the three doses of COVID-19 vaccines. 210 participants were analyzed after administering any doses of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterol-ogous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to ho-mologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has become an unprecedented challenge to global public health. With the intensification of the COVID-19 epidemic, the development of vaccines and therapeutic drugs against the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are also widespread. To prove the effectiveness and safety of these preventive vaccines and therapeutic drugs, available animal models that faithfully recapitulate clinical hallmarks of COVID-19 are urgently needed. Currently, animal models including mice, golden hamsters, ferrets, nonhuman primates and other susceptible animals have been involved in the study of COVID-19. 92 vaccine candidates have entered clinical trials after the primary evaluation in animal models, of which inactivated vaccines, subunit vaccines, virus-vectored vaccines and mRNA vaccines are promising vaccine candidates. In this review, we summarize the landscape of animal models and advanced vaccines with efficacy range from about 50% to more than 95%. In addition, we point out future directions for animal models and vaccine development, aiming at providing valuable information and accelerating the breakthroughs confronting SARS-CoV-2.

With the arrival of SARS-CoV-2 vaccines, a new stage of the pandemic commenced, with new challenges ahead. During the coming months, countries will be implementing their COVID-19 vaccination programs depending on their implementation of vaccine availability and its prescription on risk stratification. Although children will not benefit from active immunization programs, now, with the beginning of the era of the anti-COVID19 vaccines, the suffering of children can no longer be ethically tolerated or neglected. The time has come to provide specific lasting strategies for children living in the COVID-19 era. Here we propose a child-focused indirect COVID-19 vaccination strategy.For better or worse, children depend on their natural caregivers (adults) and the rest of society for their well-being and achieving their full potential. We believe that including in the priority categories also those adults in close contact with children could ensure a safety net of child protection.A child-focused vaccination strategy would allow the faster return to "normality" for children and their families. Such an approach would not only enable the reopening and continuity of essential services for children but also would allow adults to return to their routine economic/productive activities.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

Using publicly available data for 28 EU/EES countries from Eurostat and Our World in Data, we investigate how the current rate of Covid vaccination in a country compares to its average rate of excess mortality (EM) in the pandemic to date. We find that, in the linear regression, the correlation between average EM and vaccination rate is strongly negative, a priori evidence to support the claim that the Covid vaccines have saved many lives. However, a closer analysis of the timeline suggests otherwise. The correlation was already strongly negative before the vaccines were rolled out and is only weakly negative thereafter. In theory, survivor bias could still explain this shift, especially since waves of EM closely align with Covid waves. However, we find in addition that about half of our 28 countries experienced higher EM in 2022 than in 2021, and all that did so have higher than average vaccination rates. This is something which survivor bias cannot explain and raises the real possibility that the vaccines have not just failed to save many lives, but may have already caused net harm. Moreover, any such harm may be ongoing since we find that EM and vaccination rates have been consistently positively correlated since April 2022. We show that all these findings are robust to several different ways of measuring EM and/or vaccination rates. Finally, using public data from Worldometers, we show that the correlation over time of official Covid mortality rates with current vaccination rates closely tracks that of EM rates, even as Covid mortality has waxed and waned and even in the post-omicron period.

SARS-CoV-2 infections underlie the current Coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. Mortality risk from severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n=166) from COVID-19 patients (n=33) were collected consecutively and analysed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r=0.7758, p<0.001), pointing to an insufficient Se status for optimal selenoprotein expression. In comparison to reference data from a European cross sectional analysis (EPIC, n=1915), the patients showed a pronounced deficit in total serum Se (mean±SD, 50.8±15.7 vs. 84.4±23.4 µg/L) and SELENOP (3.0±1.4 vs. 4.3±1.0 mg/L). A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors (Se; 53.3±16.2 vs. 40.8±8.1 µg/L, SELENOP; 3.3±1.3 vs. 2.1±0.9 mg/L). We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion on a relevant role of Se for COVID convalescence, and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

Rare cardiac adverse events are reported post vaccinations. For the SARS-CoV-2 vaccines, higher numbers of these cardiac adverse events are being reported with myocarditis disproportionately occurring in younger males. The etiology of these cardiac adverse events associated with vaccines including SARS-CoV-2 is unknown. The etiology of the higher frequency of these cardiac adverse events temporally associated with SARS-CoV-2 vaccines is also unknown. This article proposes that innate immune responses to vaccines cause elevated histamine levels post vaccination; the histamine level reached may exceed the vaccinees’ histamine tolerance level for several days. This article proposes that the elevated histamine level is causative for the reported cardiac adverse events. For myocarditis reported adverse events, this article proposes that elevated histamine levels induce cardiac capillary pericyte induced vasoconstrictions followed by localized ischemia and anoxia; this is followed by the release of troponin from myocyte cells affected by anoxia. This hypothesis is supported by the temporal onset timing of adverse events reported following SARS-CoV-2 vaccinations in the United States Department of Health and Human Services Vaccine Adverse Event Reporting System (VAERS). This model applies to multiple vaccines with innate immune response histamine levels generated varying by each vaccine and incidence frequencies correlate with vaccine reactogenicity.

The question of how many deaths were averted by interventions during the COVID-19 pandemic carries important implications for policies going forward. Given that the interventions of lockdowns and mass vaccination carry acknowledged downsides, it is important to balance these against potential upsides, which were the putative reasons for health officials to implement these policies. Several attempts have been made to quantify the impact of mass vaccination on averted mortality both globally, and in specific countries/regions, using different methodologies. Here, we examine the assumptions of these models and look for areas of improvement, while understanding that simplifications are inherent in model building. We find that several assumptions greatly overstate the degree of averted mortality due to vaccination and perform an empirical analysis of country level data in Europe to test if vaccination was associated with lower excess mortality. We show a positive and statistically significant correlation between number of vaccine doses given and 2022 excess mortality, calling into question estimates of positive averted mortality due to mass vaccination. Our results show several assumptions which work to systematically overstate the level of averted mortality from Covid-19 vaccines. This work aims to improve epidemiological modeling on the impact of vaccination, and to ground the public health response to infectious diseases in robust and rigorous analysis.

In this review, we address issues that relate to the rapid “Warp Speed” development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of “Warp Speed” immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the “Warp Speed” vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.

As a result of the spread of SARS-CoV-2, a global pandemic was declared. Indiscriminate COVID-19 vaccination has been extended to include age groups and naturally immune people with minimal danger of suffering serious complications due to COVID-19. Solid immuno-histopathological evidence demonstrates that the COVID-19 genetic vaccines can display an off-target distribution in tissues that are terminally differentiated, triggering autoimmune reactions. These include the heart and brain, which may incur in situ production of spike protein eliciting a strong autoimmunological inflammatory response. Due to the fact that every human cell which synthesizes non-self antigens becomes inevitably the target of the immune system, and since the human body is not a strictly compartmentalized system, accurate pharmacokinetic and pharmacodynamic studies are needed in order to determine precisely which tissues can be harmed. Therefore, our article aims to draw the attention of the scientific and regulatory communities on the critical need of bio-distribution studies for the genetic vaccines against COVID-19, as well as of rational harm-benefit assessments by age group.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

Abstract The emergence of mRNA vaccines represents a significant advancement in public health by conferring protection against a variety of infectious diseases. However, concerns regarding the potential risk of inducing or exacerbating autoimmune disorders, particularly connective tissue diseases (CTDs), have arisen. This paper explores the mechanisms by which mRNA vaccines may lead to the onset or worsening of CTDs, focusing on the immune responses induced by Pathogen-Associated Molecular Patterns (PAMPs), the interactions between Toll-like receptors 7/8 and 9 (TLR7/8 and TLR9), and the activation of self-reactive B cells. Furthermore, guidelines are suggested for administering vaccines to individuals at elevated risk, such as those with a positive antinuclear antibody (ANA) test or specific rheumatic disease genes. Our findings underscore the necessity for targeted vaccination strategies that mitigate risks while maintaining public health efficacy.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

We were tasked by Canada’s COVID-19 Immunity Task Force to describe severe adverse events (SAE) associated with emergency department (ED) visits and/or hospitalizations in immune-mediated inflammatory diseases (IMID). At 8 Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; mean age was 52.5 years. BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. Forty-nine percent of participants had IBD, 27.4% RA, 14.3% PsA, 5.3% SpA, and 4% SLE. Twelve SAEs leading to ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included 6 ED visits (including one Bell’s Palsy 31 days after first vaccination) and 6 hospitalizations (including one Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs involved pericarditis, one in SLE (considered a serious disease flare) and one in RA. Thus, in the 31 days after SARS-CoV-2 vaccination in IMID, though several serious AEs occurred, these were relatively few. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

The aims of the study are: a) Describe the reactogenicity of WHO-approved two mRNA (Pfizer-BioNTech, Moderna) and two non-RNA vaccines (Oxford-AstraZeneca, Sinovac) among lactating mother and baby pairs; and b) compare and contrast the reactogenicity between mRNA and non-mRNA vaccines. A cross-sectional, self-reported survey was conducted amongst 1784 lactating women who received COVID-19 vaccinations. The most common maternal adverse reaction was a local reaction at the injection site; the largest minority of respondents, 43.7% (780/1784), reported experiencing worse symptoms when receiving the second dose compared to the first dose. There were no major reported adverse effects or behavioural changes in the breastfed infants. Among the respondents who received non-mRNA COVID-19 vaccinations, a majority reported no change in lactation but those who did more commonly reported an increase in milk supply, decrease in milk supply and pain in the breast. The more commonly reported lactation changes (fluctuations in breastmilk supply and pain in the breast) for the non-mRNA vaccines were similar to that of respondents who received mRNA vaccines. Our study, with a large cohort and wide geographical and racial mix, further augments earlier reported findings that COVID-19 vaccines are safe for breastfeeding mothers and her children.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the development of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs.; (2) Methods: Single-center retrospective study in patients with ADRs post-mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines).; (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculo-papular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular lympho-histiocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred post-second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% and maculo-papular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients.; (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. The majority of ADRs are self-limited with a few extending beyond a month.

BACKGROUND: Is pharmacovigilance at a moment of prominence for science and in relation to government responsibilities towards their nations, as the new coronavirus pandemic has surprised everyone in a negative and lethal way. OBJECTIVE: Evaluate pharmacovigilance as a resource for controlling and understanding the adverse effects caused by vaccines in use. DESIGN AND SETTING: Narrative review developed by a research group at Faculty of Medicine of the University of Porto. METHODS: This is a narrative review of the literature available in electronic media, government bulletins and similar bodies. The search was carried out using the descriptors: "Pharmacovigilance AND COVID-19 in Brazil", "Vaccine Development AND COVID-19 in Brazil", "Vaccination Hesitancy AND COVID-19 in Brazil", "Pharmacovigilance AND COVID-19", "Vaccine Development AND COVID-19", "Vaccination Hesitancy AND COVID-19", Pharmacovigilance AND COVID-19, Vaccine Development AND COVID-19, Vaccination Hesitancy AND COVID-19, "Public Health Surveillance AND COVID-19". In the period from May 2021 to June 2022. RESULTS: From the database search, 3 journal articles, 4 government bulletins and 535 scientific articles were identified. Of the total of 542 bibliographic materials, 36 were selected according to the selection criteria and objectives of the study. CONCLUSIONS: The vaccines in use have proven efficacy, despite adverse reactions that cannot be attributed solely and exclusively to their use, since the medical history of each patient should be considered in the investigation of each case, especially when there is death. The Brazilian data for adverse events, although the country is continental in its size, are acceptable given the number of deaths recorded.

Background: The duration of the vaccine's protective efficacy against SARS-CoV-2 is unknown. Evaluation of the clinical performance of available tests is required. Objectives: To evaluate the clinical performance of three immunoassays for the detection of IgG antibodies generated by mRNA vaccines against SARS-CoV-2. Methods: Two automated immunoassays (Euroimmun Anti-SARS-CoV-2 ELISA IgG and Abbott SARS-CoV-2 CLIA IgG) and one lateral flow immunoassay (LFIA Test Livzon IgG) were tested. 300 samples distributed in 3 groups were analyzed: 100 subjects over 18 years old and under 45 years old, 100 subjects between 45-65 years old and another 100 over 65 years old. collected before vaccination, at 21 days, 1, 2, 3 and 6 months post-vaccination. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and agreement (I. Kappa) were calculated for each serological test. Results: Maximum sensitivity for IgG was 98.7%, 98.1%, and 97.8% for the ELISA Euroimmun, CLIA Abbott, and Livzon LFIA assays and maximum specificity for IgG was 99.4%, 99.9%. % and 98.4% ELISA, CLIA and LFIA respectively at 3 months after vaccination with a decrease in antibody levels from the sixth month. The best agreement was observed between ELISA and CLIA 100%; (k = 1.00). The agreement between ELIA, CLIA and LIFIA was 99% (k = 0964) at the second and third month after vaccination. Seroconversion was faster and longer lasting in the younger age groups. Conclusion: Our study showed an equivalent and homogeneous clinical performance for IgG of three immunoassays after vaccination and that the LIFIA assay is the most cost-effective, reliable and accurate for routine use in population studies of seroconversion and seroprevalence.

A novel coronavirus (SARS-CoV-2), causing an emerging coronavirus disease (COVID-19), first detected in Wuhan City, Hubei Province, China has resulted in an outbreak in China which has taken a catastrophic turn with high toll rates in China and subsequently spreading across the globe. The rapid spread of this virus to more than 175 countries while affecting nearly 500,000 persons and causing more than 22,000 human deaths, it has resulted in a pandemic situation in the world. The SARS-CoV-2 virus belongs to the genus Betacoronavirus, like MERS-CoV and SARS-CoV, all of which originated in bats. It is highly contagious, causing symptoms like fever, dyspnea, asthenia and pneumonia, thrombocytopenia and the severely infected patients succumb to the disease. Coronaviruses (CoVs) among all known RNA viruses have the largest genomes ranging from 26 to 32 kb in length. Extensive research has been conducted to understand the molecular basis of the SARS-CoV-2 infection and evolution, develop effective therapeutics, antiviral drugs and vaccines, and to design rapid and confirmatory viral diagnostics as well as adopt appropriate prevention and control strategies. Till date, no clinically proclaimed, proven therapeutic antibodies or specific drugs and therapeutics, and vaccines have turned up. Several molecular diagnostic tests such as Real Time-PCR, isothermal loop-mediated amplification of coronavirus (i-LACO), full genome analysis by next-generation sequencing (NGS), multiplex nucleic acid amplification, and microarray-based assays are in use currently for the laboratory confirmation of this CoV infection. In this review article, we describe the basic molecular organization and phylogenetic analysis of the coronaviruses, including the SARS-CoV-2, and recent advances in diagnosis and vaccine development in brief and focusing mainly on developing potential therapeutic options that can be explored to manage this pandemic virus infection, which would help in valid countering of COVID-19.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

How to optimally allocate COVID-19 vaccines and scarce public goods is a crucial and sensitive question to scholars, policy-makers, and practitioners. The ethical dimensions and principles of vaccine allocation between groups are widely agreed upon, whereas the ethical dimensions and principles of vaccine distribution between countries at the peak of the COVID-19 pandemic are highly controversial. This article aims to investigate how vaccines were globally allocated across countries and propose an optimal allocation mechanism for vaccines and scarce public goods. The results show that, to a certain extent, the global allocation of COVID-19 vaccines was fair and effective. Countries with more cases and deaths obtained more vaccines and vaccinations. Wealthier countries might receive more vaccinations but also suffer more severe consequences of COVID-19. Though COVAX could miss its initial vaccine delivery targets, the facility should be considered successful in its core goals and plays a critical role in controlling the pandemic. The study proposes a fair and effective mechanism of vaccine allocation that combines the roles of markets and interventions of international organizations and national governments with three degrees: emergency, priority, and market.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic which has been a topic of major concern to global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7, B.1.351, P1 and, B.1.617., which show in-creased transmissibility and resistance towards vaccines and therapies. Importantly, the likelihood of susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response or comorbidities needs greater attention. Herein, we provide a comprehensive perspective regarding ongoing vaccine (mRNA, protein-based, viral vector based etc.) and therapeutic (mono-clonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.

Background: Although confirmed cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been declining since late 2020 due to general vaccination, little research has been done regarding the impact of vaccines against SARS-CoV-2 in Spain in terms of hospitalizations and deaths. Objective: Our aim was to identify the reduction in severity and mortality of coronavirus disease 2019 (COVID-19) at a nationwide level due to vaccination. Methods: We designed a retrospective, population-based study to define waves of infection and to describe the characteristics of the hospitalized population. We also studied the rollout of vaccination and its relationship with the decline in hospitalizations and deaths. Finally, we developed two mathematical models to estimate non-vaccination scenarios using machine learning modeling (with the ElasticNet and RandomForest algorithms). The vaccination and non-vaccination scenarios were eventually compared to estimate the number of averted hospitalizations and deaths. Results: In total, 498,789 patients were included, with a global mortality of 14.3%. We identified six waves or epidemic outbreaks during the observed period. We established a strong relationship between the beginning of vaccination and the decline in both hospitalizations and deaths due to COVID-19 in all age groups. We also estimated that vaccination prevented 170,959 hospitalizations (CI 95% 77,844–264,075) and 24,546 deaths (CI 95% 2,548–46,543) in Spain between March 2021 and December 2021. We estimated a global reduction of 9.19% in total deaths during the first year of COVID-19 vaccination. Conclusions: Demographic and clinical profiles changed over the first months of the pandemic. Patients over 80 years old and other age groups obtained clinical benefit from early vaccination. The severity of COVID-19, in terms of hospitalizations and deaths, decreased due to vaccination.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

There exists a compelling need to better understand the temporal dynamics of public sentiment towards COVID-19 vaccines in the US on a national and state-wise level for facilitating appropriate public policy applications. Our analysis of social media data from early February of 2021 and late March of 2021 shows that in spite of overall strength of positive sentiment, and increasing numbers of Americans being fully vaccinated, negative sentiment about COVID-19 vaccines still persists among sections of people who are hesitant towards the vaccine. In this study, we performed sentiment analytics on vaccine tweets, studied changes in public sentiment over time, conducted vaccination sentiment validation using actual vaccination data from the US CDC and Household Pulse Survey (HPS), explored influence of maturity of Twitter user-accounts and generated geographic mapping of sentiments by location of Twitter users. Furthermore, we leverage the emotion polarity based Public Sentiment Scenarios (PSS) framework which was developed for COVID-19 sentiment analytics, to systematically analyze directions for public policy processes to potentially improve the administration of vaccines. Application of the PSS framework provides important time sensitive insights for state and federal government agencies and associated organizations to better implement public policy processes for healthcare management, communication, transparency, motivation and societal operational policies such as social distancing. These insights are expected to contribute to processes that can expedite the vaccination program and move closer to the cherished herd immunity goal.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development; nevertheless, concerns of the experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

COVID-19 has become a severe global public health concern. The critical illness has a mortality rate of 61.5%, and thus, reducing the severity and mortality is top priority. Currently, inflammatory storms are considered as the cause of critical illness and death due to COVID-19. However, After systematical review of the literature, we proposed that cross-reactive antibodies-associated antibody-dependent enhancement (ADE) may actually be the cause of cytokine storms. If the activation of memory B cells can be selectively inhibited in high-risk patients at an early stage of COVID-19 to reduce the production of cross-reactive antibodies of the virus, we speculate that the ADE can be avoided and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such conditions. We recommend that pharmaceutical companies conduct clinical trials urgently.

In this age of mass media and, in particular, social media-driven perception of reality, coupling disease and prophylactic opinion dynamics models can provide better insights into disease evolution than using a disease model alone. We develop in this work two disease-opinion dynamics models based on the epidemiology of the new coronavirus disease (COVID-19) and the availability or not of imperfect vaccines. We assume that susceptibility to infection decreases with the level of prophylactic attitude (personal hygiene, social distancing), and changes in prophylactic attitudes of susceptible individuals occur in response to perceived disease prevalence and vaccination coverage and efficacy in the population. We derive and discuss the disease-free equilibriums and reproduction numbers in the introduced models. We further assess the impacts of the distribution of opinions at disease introduction, the ability to detect presymptomatic, asymptomatic and symptomatic positive COVID-19 cases, the behavioural responses to the outbreak and the introduction of vaccination, and the effects of distortions of disease prevalence by public policy and mass media on disease dynamics. The insights highlighted from the proposed models are expected to make informative contributions to public policy in a context of opinion fluxes in response to perceived disease prevalence.

Vaccination against the SARS-CoV2 virus has shown great promise in managing the spread and severity of Covid-19. While these vaccines were able to provide a favourable response in controlling the SARS-CoV2 infection, its use came with accompanying side effects. This systematic review aimed to determine the effectiveness of the different Covid-19 vaccine subtypes and discover the side effects associated with each vaccine elsewhere but specially in Trinidad and Tobago. For this systematic review, the keywords “Pfizer-BioNTech OR Moderna OR Oxford-AstraZeneca OR Janssen OR Sinopharm OR Novavax AND Covid-19 vaccine efficacy” and “Covid-19 vaccines AND Trinidad and Tobago” were researched under PubMed, MEDLINE and other internet sources through which other notable journals, and documents were discovered and searched similarly as outlined previously. In doing so, 65 relevant articles were included as part of this review. Of the studies examined, overall the vaccine with the greatest VE was found to be Pfizer-BioNTech (95%), followed by Moderna (94.1%), Novavax (89.7%), AstraZeneca (70.4%), Sinopharm (67%) and finally Janssen (66.9%). The use of Pfizer-BioNTech or Moderna was most efficacious in response to the different Covid-19 variants. Some side effects were common for all vaccine types however adverse effects were more commonly seen with vaccination by mRNA vaccines, Pfizer-BioNTech and Oxford-Astrazeneca. Researchers targeted individuals aged 18 and above residing in various geographical areas of TT, specifically focusing on those who had not received the COVID-19 vaccine and expressed hesitancy towards it. Convenience sampling was used to select the study participants, and formal in-depth virtual interviews were conducted on a one-to-one basis, employing a semi-structured questionnaire to guide the discussions. The interviews were meticulously recorded and transcribed, following the principles of reflexive thematic analysis, to distill key insights from the participants' responses. The study's findings, derived from the perspectives of 25 participants, illuminated a complex tapestry of reasons underlying vaccine hesitancy in Trinidad and Tobago. Notably, prominent themes emerged, including fear, doubts regarding vaccine efficacy, a perceived inadequacy of information, a sense of susceptibility to the virus, deep-seated mistrust, alternative herbal remedies, and religious reservations. Interestingly, the motivations expressed by these vaccine-hesitant individuals for potentially receiving the vaccine in the future were rooted in notions of necessity, an increased sense of susceptibility to the virus, a desire to reach a certain health benchmark, and a need for assurance regarding the vaccine's safety and effectiveness. This comprehensive exploration of vaccine hesitancy in TT provides valuable insights for public health officials and policymakers in crafting targeted strategies to address this critical issue within the local context. Conclusion: The findings of this study determined that vaccination against the SARS-CoV2 virus provided beneficial outcomes against infection, Covid-19 related hospitalizations, ICU admissions and mortality. While vaccination was deemed highly appropriate in managing the spread of the SARS-CoV2 virus and enhancing the outcomes in infected persons, the effectiveness of the different vaccine platforms indicated that certain vaccine platforms are preferential to others in different populations. In terms of vaccine efficacy, nucleic acid vaccines such as Pfizer-BioNTech and Moderna showed the greatest effectiveness while inactivated whole virus vaccines such as Sinopharm and viral vectors like Janssen had the least effectiveness. The side effects, joint/muscle soreness, pain at the injection site, shoulder pain, headaches, fever, chills, weakness, epistaxis, renal and certain cardiovascular events were common for all vaccine types. Adverse effects were more frequent and severe with the mRNA vaccines by Pfizer-BioNTech and Oxford-Astrazeneca than inactivated whole virus vaccines. The data collected in this research can be very useful to help individuals make a decision on which vaccine would be appropriate for them. More long-term studies are needed to better gauge the scope of side effects for each vaccine type.

Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.

This prospective cohort study aimed to evaluate the efficacy of COVID-19 vaccine schemes, ho-mologous versus heterologous vaccine strategies, and vaccine-induced anti-S-RBD-IgG antibody response in preventing COVID-19 among 942 healthcare workers one year after vaccination with the inactivated and/or mRNA vaccines. All participants received the first two primary doses of vaccines, 13.6% of them lacked the dose-3, 50.5% the dose-4, and 90.3% the dose-5. Antibody lev-els increased with the increase in number of vaccine doses and also in heterologous vaccine regi-mens. In both inactive and mRNA vaccines, infection rates were significantly higher in 2-dose-receivers, but lower in 4- or 5-dose receivers and increasing the total number of vaccine doses resulted in more protection against infection: the 3-dose regimen yielded 4.71 times more protection, the 4-dose 11.76 times and 5-dose 38.46 times more protection from COVID-19 infec-tion, compared to any 2-dose vaccination regimens. Antibody levels at the end of the first year of 4- or 5-dose-receivers were significantly higher than 2- or 3-dose-receivers. To conclude; increased number of total vaccine doses and anti-S-RBD antibody levels increased the protection from COVID-19 infection. Therefore, four or more doses are recommended in one year, for effective protection, especially in risk groups.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

Since the beginning of the mass immunization with COVID-19 vaccines of patients with multiple sclerosis, many data on the efficacy and safety of these vaccines have been produced. Considering that MS is an autoimmune disease whose pathology can be explained by an altered immune system and that some DMTs seem to be able to decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety in terms of AEFIs occurrence and the antibody response after the third dose of COVID-19 vaccines in people with MS. Third doses were administered from October 2021 to January 2022. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. The majority of patients (n=193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

In our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart. Here we investigated if psychological factors (distress, anxiety and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination. Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including stage of metastatic disease and high stress levels (OR=2.46, 95% CI, 1.05-5.77, p=0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p=0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months (p=0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 month time (p=0.03). The data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts (p=0.0004). At baseline, the high discomfort rate (≥5) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, higher educational level was related to increased distress among women (p=0.046). These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.

Since the first description of SARS-CoV-2 in China in 2019, thousands of variants have emerged worldwide. For some of them, the constellation of mutations caused changes in virus biology, pathogenicity, infectivityity and transmissibility resulting in dissemination throughout the world. Gamma variant (P.1) differs from SARS-CoV-2 Wuhan strain (B.1) by 12 amino acids in the Spike (S) protein, and presented mutations related to greater affinity for the receptor angioten-sin-converting enzyme 2 (ACE-2) and/or immune escape. The Gamma variant and subvariants were responsible for the second wave of COVID-19 in the Brazilian city of Manaus, characterized by high mortality and rapid transmission. The ability of variants to induce cytokine production may be closely related to their pathogenicity. Herein we observed that there was no significant difference in the quantity of cytokines among macrophages or neutrophils infected with P.1 and B.1 strains. Also, no significant difference was observed in the absolute number of macrophages and neutrophils infected with these variants. Furthermore, no evidence of SARS-CoV-2 replication was observed in macrophages when infected by the two analyzed variants. Our findings suggest that the difference in the epidemiological outcome observed during the P.1 variant spread when compared to B.1, it is not explained by differences in the quantity of cytokines and absolute number of macrophages or neutrophils. Through bioinformatics analysis of the S protein, we observed that the physicochemical differences between the variants and subvariants of P.1, probably refer to the degree of infectivity, due to the impact caused in the recognition of antibodies and receptor af-finity

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), coronavirus disease 2019 (COVID-19)-induced infection is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding, often occurs in subjects with weak multiple risk factors and co-morbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (vWF). Central to activity of these biomarkers are their receptors and signaling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19, and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of vWF, P-selectin and fibrinogen are present with still low levels of D-dimer. Progression to vWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devises and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

Global severity maps of ongoing dengue epidemic and COVID-19 pandemic do not overlap. Countries with high dengue endemicity (>1.5 million cases/year) are observably less hit by COVID-19 in terms of infection, transmission and mortality. Based on non-overlap of dengue and COVID-19 severity maps and evidence of SARS-CoV-2 serological cross-reactions with dengue, we wonder whether immediate immunization of susceptible populations in Europe, North America and Asia (China, Iran) with available live-attenuated dengue vaccines, will cue the anti-viral immune response to thwart COVID-19 (viral interference). Risk of developing post-vaccination “Antibody-dependent Enhancement” is low as dengue is not endemic in the aforesaid regions.

Global research on the Covid-19 vaccine’s effectiveness is using methods that are misleading the scientific community and public opinion. There is a golden rule in medicine: to measure the effectiveness of an experimental medicine you need to have two groups. The group that will take medicine and the group that will not take medicine. You follow the health status of both groups for a few months and you will get objective results. This is the only proper methodology to verify the effectiveness of a new medicine. Articles cited from 1-5 did not use the gold rule. They develop different kinds of methodologies that all have no statistical significance. On the basis of their methodologies, they conclude that Covid-19 vaccines have a positive effect on public health. By comparing graphs of the intensity of vaccination and the rate of mortality we see that after the period of intense vaccination follows the period of higher excess mortality. Basic statistical data are confirming that Covid-19 vaccines increased the mortality rate.

Background/Objectives: The COVID-19 pandemic has significantly impacted global health, with varying vaccine effectiveness (VE) across different regions and vaccine platforms. In Africa, where vaccination rates are relatively low, inactivated vaccines like Sinopharm and Sinovac have been widely used. This study evaluated the real-world effectiveness of licensed inactivated COVID-19 vaccines in Zimba-bwe during a period dominated by Omicron variants. Methods: We conducted a prospective test-negative case-control study among symptomatic adults across six Zimbabwean provinces from November 2022 to October 2023. Participants were categorized based on vaccination status, and na-sopharyngeal swabs were collected for SARS-CoV-2 PCR testing. Vaccine effective-ness was assessed using conditional logistic regression, adjusting for various co-variates such as age, sex, and comorbidities. Results: Among 5,175 participants, 701 tested positive for SARS-CoV-2, and 4,474 tested negative. The overall adjusted VE against symptomatic COVID-19 was 31% (95% CI: 5.3%-49.7%) among verified vaccinated individuals. Boosted individuals demonstrated a higher VE of 59.8% (95% CI: 40.3%-72.9%). VE decreased signifi-cantly to 24% (95% CI: -4.1%-44.8%) in individuals vaccinated over a year prior. Similar VE was observed for Sinopharm (36.8%, 95% CI: 11.4%-54.9%) and Sino-vac (38.1%, 95% CI: 16.3%-54.2%). Conclusions: The study indicates modest protection from inactivated COVID-19 vaccines against symptomatic Omicron infection, with significant enhancement fol-lowing booster doses. These findings highlight the need for continued vaccine eval-uation, particularly in resource-limited settings, to inform public health strategies and optimize vaccination programs.

Aim: To evaluate the impact of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence, obstetrical and perinatal outcomes, and costs, as compared to the standard diagnostic method. Methods: A cohort of pregnant individuals undergoing GMD screening with the alternative GDM method, which uses plasma glucose (fasting or non-fasting) and HbA1c, was compared with a cohort of pregnant individuals undergoing the standard GDM screening method. Both cohorts were obtained from 6 hospitals across Catalonia, Spain, from April 2020 to April 2022. The primary outcome was large for gestational age rate at birth. Secondary outcomes were composite adverse outcomes including pregnancy complications, delivery complications, and neonatal complications. Cost differences between screening methods were also evaluated. A similar analysis was performed in the subgroup diagnosed with GDM. Results: Data were collected from 1,543 pregnant individuals in the standard screening group and 2,197 in the alternative screening group. The standard screening group had a higher GDM diagnostic rate than the alternative screening group (10.8% vs 6.9%, respectively; p<0.0001). The primary outcome (large for gestational age rate) was similar between groups: 200/1543 (13.0%) vs 303/2197 (13.8%). The adjusted OR for this outcome was 1.74 (95% CI: 0.74-4.10). An adjusted analysis showed no differences between groups in composite adverse outcomes for pregnancy complications (OR: 1.11; 95% CI: 0.91-1.36), delivery complications (OR: 0.95; 95% CI: 0.75-1.19), and neonatal complications (OR: 1.28; 95% CI: 0.94-1.75). Among individuals diagnosed with GDM, the large for gestational age rate was similar between groups: 13/166 (7.8 %) vs 15/151 (9.9 %). The OR adjusted for this outcome was 1.24 (95% CI: 0.51-3.09). An adjusted analysis showed no differences in composite adverse outcomes for pregnancy complications (OR: 1.57; 95% CI: 0.84-2.98), delivery complications (OR: 1.21; 95% CI: 0.63-2.35), and neonatal complications (OR: 1.35; 95% CI: 0.61-3.04). The mean cost (which included expenses for consumables, equipment and personnel) of the alternative screening method was 46.0 euros (22.3 SD), as compared to 85.6 euros (67.5 SD) for the standard screening method. Conclusions: In this Spanish population during the COVID-19 pandemic, GDM prevalence was lower in the alternative screening group than in the standard screening group. After adjusting for GDM risk factors, outcomes related to obstetrics, delivery, and neonatal complications were comparable between both groups. Finally, the alternative screening method was cheaper than the standard screening method.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccines-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and literature review another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine groups (viral vector, mRNA and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccines-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including 15 patients (19%) with anti-MOG, 11 (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than other groups. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. The research suggests potential associations between COVID-19 vaccines-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific groups.

The COVID-19 pandemic has had a significant impact on every individual in the United States. The launch of the COVID-19 vaccines is estimated to have averted millions of deaths and reduced over 18 million COVID-19 related hospitalizations. In September 2023, the updated 2023-2024 COVID-19 vaccine that include a monovalent component that corresponding to the omicron variant XBB.1.5 reflecting the predominant circulating variant at the time of strain selection, was approved and was recommended for use in all people ≥ 6 months of age. Despite this recommendation, the US uptake of the updated COVID vaccines over the 2023-2024 season has been far from optimal, placing many people at unnecessary risk of severe COVID-19 outcomes. This paper provides an overview of the current state of COVID-19 in 2023-2024, and barriers to vaccine uptake. With the continued evolution of the virus, the potential for more virulent variants and the lower public acceptance of vaccination, the potential barriers that contributed to low vaccine uptake are explored, as well as to provide solutions for improving COVID-19 protection for future seasons.

Researchers and organizations are pursing 100 Day Vaccine Development to reduce the impact of any new pandemic-causing virus. They propose monitoring viral emergence and developing vaccines for discovered viruses which would undergo safety testing in humans. If one of these viruses emerges, phase III trials would then take place. There are two problems with this approach - first, phase III trials are too long for the 100-day goal and second, the virus that emerged might not have been discovered in their surveillance. An alternative approach would be to first develop vaccines for viral families similar to the pan coronavirus vaccines being proposed for next generation COVID vaccines. Phase III trials for them would be run even if a virus in the family wasn’t having an outbreak. If a virus in a family for which a vaccine has been developed has an outbreak and the phase III trialed vaccine is not effective against it, develop a booster based on the phase III trialed vaccine. Since booster development and approval takes less than 100 days, the 100 Day Vaccine Development goal would be met.

This study examines the association of sociodemographic risk factors and the comorbidities of COVID-19. Most COVID-19-related studies were conducted in inpatient settings among patients with severe infection during the first and second waves of the pandemic. The third wave with less severe Omicron variant presented a unique opportunity to observe the adult patients treated in outpatient settings. We conducted a cross-sectional study (117 patients aged &gt; 40 years presented with symptomatic COVID-19). We employed the Charlson Comorbidity Index (CCI) to compute comorbidity burden, Medical Outcomes Survey Short form (SF-12) to measure general health, and Self-care Self- Efficacy Scale (SCSES) to assess self-care ability. Fisher’s exact test and analysis of variance (ANOVA) were used to compute the relationship between comorbidities and demographics. This study report focuses on the distribution of the comorbidities and its relationship to demographic variables. The top five comorbidities were hypertension (42%), diabetes (31%), pulmonary disease/asthma (19%), depression (14%), and cancer (11%). Depression was significantly higher among younger age groups (p&lt;0.01) and women (p&lt;0.05). Age (p&lt;0.0001) and income (p&lt;0.01) were the most significantly associated demographics with the comorbidity burden. Incidence of pulmonary disease showed a positive association to educational status (p=0.05). This was the first study to report a significant prevalence of depression among adults with symptomatic COVID-19.

Introduction: In Part I of this three-part series we report a retrospective, population-based cohort study assessing rates of adverse events (AEs) in pregnancy after COVID-19 vaccines compared to the same AEs after influenza vaccines and after all other vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and prevention (CDC) and the U.S. Food and Drug Administration (FDA). The CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024, for adverse events (AEs) involving pregnancy complications following COVID-19 vaccination. The time-period included 412 months for all vaccines except COVID-19 vaccines, having been used for only 40 of the 412 months (December 1, 2020, to April 26, 2024). Proportional reporting ratios (PRR) by time compared AEs after COVID-19 vaccination to those after influenza vaccination, and after all other vaccine products administered to pregnant women. In cases in which the PRR was not applicable, Chi-square analysis and Fisher’s exact tests were used according to CDC/FDA guidance. CDC/FDA stipulate a safety concern if a PRR is ≥ 2 or if a Chi-square is ≥ 4. Results: The CDC/FDA’s safety signals were breached for all 37 AEs following COVID-19 vaccination in pregnancy: miscarriage, fetal chromosomal abnormality, fetal malformation, cervical insufficiency, premature rupture of membranes, premature labor, premature delivery, placental calcification, placental infarction, placental thrombosis, placenta accreta, placental abruption, placental insufficiency, placental disorder, fetal maternal hemorrhage, fetal growth restriction, reduced amniotic fluid volume, preeclampsia, fetal heart rate abnormality, fetal cardiac disorder, fetal vascular mal-perfusion, fetal arrhythmia, fetal distress, fetal biophysical profile abnormal, hemorrhage in pregnancy, fetal cardiac arrest, fetal death (stillbirth), premature infant death, neonatal asphyxia, neonatal dyspnea, neonatal infection, neonatal hemorrhage, insufficient breast milk, neonatal pneumonia, neonatal respiratory distress, neonatal respiratory distress syndrome, and neonatal seizure. All p values were ≤ 0.001 with the majority being <0.000001. Summary statistics for the deviation from the CDC/FDA safety signals mean (n, range) are as follows: PRR 69.3 (46, 5.37 - 499); z statistic 9.64 (46, 3.29 - 27.0); and Chi-square was 74.7 (26, 28.9 - 148). Conclusions: We found unacceptably high breaches in safety signals for 37 AEs after COVID-19 vaccination in pregnant women. An immediate global moratorium on COVID-19 vaccination during pregnancy is warranted. The United States government, medical organizations, hospitals, and pharmaceutical companies have misled and/or deceived the public regarding the safety of COVID-19 vaccination in pregnancy. Promotion of these products must be immediately halted.

Objective: We aim to assess the reporting discrepancy and the difference between confirmed and unreported COVID-19-like death counts.Study Design: The study is based on time-series data.Methods: We used publicly available data to explore the differences between confirmed death counts and deaths with Codiv-19 symptoms between March 8, 2020, and July 11, 2020, in Bangladesh.Results: During the week ending May 9, 2020, the unreported COVID-19-like death count was higher than the confirmed COVID-19 death count; however, it was lower in the following weeks. On average, unreported COVID-19-like death counts were similar to the confirmed COVID-19 death counts during the same period. However, the reporting authority neither considers these deaths nor adjusts for potential seasonal influenza or other related deaths, which might produce incomplete COVID-19 data and respective mortality rates. Conclusions: Documenting unreported deaths with COVID-19 symptoms needs to be included in provisional death counts because it is essential to estimate a robust COVID-19 mortality rate and to offer data-driven pandemic response strategies. An urgent initiative is needed to prepare an acceptable guideline for COVID-19 death reporting.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

The SARS-CoV-2 virus (COVID-19) has led to an initiative to develop safe and effective vaccines for public health safety. In December 2020, the United States Food and Drug Administration (FDA) administered an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine. Other vaccines from Johnson & Johnson, Moderna, and AstraZeneca shortly followed. This paper aims to examine the EUA process for COVID-19 vaccine approvals, including the requirements for the safety and efficacy of data, along with the role of the FDA and EMA in the approval process. Further, public concerns about vaccine approvals, including issues on the approval process's safety, efficacy, and speed, were also discussed. Using qualitative analysis of the extracted studies, trends and insights into the factors influencing public acceptance of COVID-19 vaccines, such as vaccine hesitancy and misinformation, were discussed. Overall, a transparent and rigorous regulatory process for vaccine approval is critical for education efforts between policymakers, vaccine developers, and the public to address concerns for increased population vaccine uptake.

The COVID-19 pandemic has exerted a significant impact on mental health globally. The uncertainty, fear, and stress associated with this crisis have contributed to a heightened prevalence of anxiety, depression, and various other mental health disorders. In this scenario, the present study aimed at investigating the relationship between locomotion regulatory mode, resilience, and COVID-19 anxiety. It is worth noting that previous extensive research has established a significant correlation between high levels of locomotion and diverse positive psychological conditions, such as optimism, reduced hopelessness, and positive affect. A total of 243 participants completed measures of locomotion regulatory mode, resilience, and COVID-19 anxiety. In line with our hypotheses, individuals' locomotion regulatory mode was negatively, although non significatively, associated with COVID-19 anxiety. Furthermore, resilience was found to mediate the relationship between locomotion regulatory mode and COVID-19 anxiety, indicating that individuals displaying high locomotion may be better equipped to cope with the stress and uncertainty of the COVID-19 pandemic due to their greater levels of resilience. Taken together, these findings highlight the importance of considering both locomotion and resilience in managing anxiety related to COVID-19 and suggest that interventions aimed at enhancing resilience may be beneficial particularly for individuals with low locomotion regulatory mode.

ACE2 impact on the severity of COVID-19 is widely discussed but still controversial. To estimate its role in aspects of the main risk factors and comorbidities, we involved post-COVID-19 patients in Ternopil region (Ukraine). Recruitment period was July 2020 to December 2021. Medical records, treatment modalities and outcomes were recorded and analyzed. Serum human ACE2 protein was measured with Cusabio ELISA kits (Houston, TX, USA). Statistical analysis was performed with SPSS21.0 software (SPSS Inc., Chicago, IL, USA). The level of ACE2 serum protein was significantly higher (p < 0.001) in patients with mild symptoms compared to more severe course of disease, and inversely had changed from 1 to 90 days after recovery. In patients with mild COVID-19, ACE2 level significantly decreased over time, while among critical patients, it increased by 34.1percent. Such results could be explained by ACE2 shedding from tissues into circulation. Loss of the membrane-bound form of the enzyme decreases the virus entry into cells. Our studies did not identify any sex-related ACE2 serum levels correlation. The most common comorbidities were hypertension, cardiovascular diseases, respiratory diseases and diabetes mellitus. All comorbidities except respiratory diseases contribute to the severity of disease and correlate with ACE2 blood serum level.

Background: Early-stage interventions in a potential pandemic are important tounderstand as they can make the difference between runaway exponential growththat is hard to turn back and stopping the spread before it gets that far. COVID-19 is an interesting case study because there have been very different outcomesin different localities. These variations are best studied after the fact if precisionis the goal; while a pandemic is still unfolding less precise analysis is of value inattempting to guide localities in the early stages to learn lessons of those that pre-ceded them. Methods: I examine three factors that could differentiate strategy: asymptomaticspread, differences in use of the Bacillus Calmette-Guerin (BCG) tuberculosis vac-cine and cloth face masks.Results:Differences in disease progression as well as the possibility of alternativestrategies to prevent COVID-19 from entering the runaway phase or damping itdown later can be elucidated by a study of asymptomatic infection. A study todemonstrate not only what fraction are asymptomatic but how contagious they arewill also inform policy on universal mask wearing. Conclusions: While a COVID-19 outbreak is at a level that makes accurate trace-and test possible, investigation of asymptomatic transmission is viable and shouldbe attempted to enhance understanding of spread and variability in the disease aswell as policy options for slowing the spread.

Introduction: In Part II of this three-part series, we expose techniques that can be used by the U.S. Centers for Disease Control and prevention (CDC) and Food and Drug Administration (FDA) to manipulate and throttle the Vaccine Adverse Event Reporting System (VAERS), a vaccine safety monitoring system open to the public. The U.S. government’s recommendation of COVID-19 vaccines during pregnancy was more a product of propaganda than of science and plagued with conflicts of interest. The extreme breach of COVID-19 vaccine pregnancy complication safety signals documented in VAERS cannot be disregarded or concealed. As a result, CDC/FDA are moving to closed, government captured platforms, including V-safe, Vaccine Safety Datalink (VSD) system, and the Biologics Effectiveness and Safety (BEST) system. Public transparency of adverse events following COVID-19 vaccination in pregnancy should be increased, not thwarted. Methods: In Part I the CDC/FDA Vaccine Adverse Event Reporting System (VAERS) database was queried from January 1, 1990, to April 26, 2024 for adverse events (AEs) involving pregnancy complications following vaccination. In Part II we investigate tactics discovered in VAERS that concealed vaccine injuries and deaths. Conflicts of interest, as well as specific communications and publications from the CDC/FDA and the New England Journal of Medicine (NEJM) are analyzed. Results: Of all VAERS AE reports, 8.47% (138,983) of COVID-19 reports had no vaccination date and thus were missing from the data presented in Part I of this series. We unconcealed data presented in Part I of this series to include VAERS case reports that were excluded when using standard queries because of an “unknown vaccination date”. The unconcealed data in the 37 AE cases reported in this study (Part II) ranged from 0 - 38% with a mean of 8.2% (standard deviation 9.7%) and the significant breaches of VAERS safety signals in Part I of this series were largely underestimated. Another method of concealing vaccine associated AEs is to exclude the specific vaccine type rendering it as an “unknown vaccine type”. “Unknown vaccine type” has logarithmically increased since the rollout of the COVID-19 vaccines in 2021, ranging from 1 to 400 cases between 1990 to 2018 to 11,461 cases in 2021. CDC/FDA granted $67 million via a Cooperative Agreement grant to Massachusetts Department of Public Health (MDPH) between July 1, 2019, to June 30, 2025. MDPH then made subawards under this grant to 21 influential public and private health and civic organizations, including NEJM’s owner, Massachusetts Medical Society (MMS). As one of the subawardees under the grant, MMS as owner of NEJM received over $426,000 in federal HHS/CDC grant money from 2019 to 2020 for “public health and medical emergency preparedness projects”. Conclusions: CDC/FDA has failed to capture and account for a significant number of AE case reports following COVID-19 in VAERS by a variety of techniques in an apparent attempt to sanitize the data. CDC’s Rochelle Walensky and NEJM’s Editor-in-Chief Eric Rubin pushed novel untested COVID-19 vaccines in pregnant women despite clear evidence from multiple sources that safety signals had been breached.

Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune mediated rheumatic disesases (IMRD) patients are scarce. This study describes breakthrough COVID-19 among IMRD patients participating of SAFER-study, a Brazilian multicentric cohort evaluating safety, effectiveness and immunogenicity of SARS-Cov-2 vaccines in autoimmune diseases. Descriptive analysis and a binary logistic regression model, to evaluate predictors of COVID-19-related hospitalization, were performed. P-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with mean (SD) age 40.23 (13.19) years. Patients received 2 (19%), 3 (70%) or 4 (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n=150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n=112) was with BNT162b2 (40%) or ChAdOx1 (26%). COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84, CI: 1.9-18.5, p=0.002) and treatment with corticosteroids (OR: 2.94, CI: 1.02-8.49, p=0.0043) associated with higher odds of hospitalization, while the increasing number of vaccine doses was protective (OR: 0.37, CI: 0.15-0.9, p=0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favour of booster vaccination in IMRD patients.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Today, we are all threatened by an unprecedented pandemic: COVID-19. How different is it from other coronaviruses? Will it be attenuated or become more virulent? Which animals may be its original host? In this study, we analyzed 377 publicly available complete genome sequences for the COVID-19 virus, the previously known flu-causing coronaviruses (HCov-229E, HCov-OC43, HCov-NL63 and HCov-HKU1) and the lethal, pathogenic P3/P4 viruses, SARS, MERS, Victoria, Lassa, Yamagata, Ebola, and Dengue. We found strong similarities between the current circulating COVID-19 and SARS and MERS, as well as COVID-19 in rhinolophines and pangolins. On the contrary, COVID-19 shares little similarity with the flu-causing coronaviruses and the other P3/P4 viruses. Strikingly, we observed divergence of COVID-19 strains isolated from human hosts has steadily increased from December 2019 to March 2020, suggesting COVID-19 is actively evolving in human hosts. From all existing human COVID-19 genome sequences, we calculated the first common model that represents the shared sequences of the human COVID-19 strains, which provides important information for vaccine and antibody development. Geographic and time-course analysis of the evolutionary trees of the human COVID-19 reveals possibly heterogeneous evolutional paths among strains from 21 countries. This finding has important implications to the management of COVID-19 and the development of vaccines.

Understanding the clinical conditions and outcomes of Covid-19 infected patients with immunodeficiency like HIV will be an information for improving management and treatment modalities. It was reported a patient of HIV plus clinical confirmed Covid-19 in this presentation.

During an epidemic outbreak it is useful for planners and responsible authorities to be able to plan ahead to estimate when an outbreak of an epidemic is likely to ease and when the last case can be predicted in their area of responsibility. Theoretically this could be done for a point source epidemic using epidemic curve forecasting. The extensive data now coming out of China makes it possible to test if this can be done using MS Excel a standard spreadsheet program available to most offices. The available data is divided up for whole China and the different provinces. This and the high number of cases makes the analysis possible. Data for new confirmed infections for Hubei, Hubei outside Wuhan, China excluding Hubei as well as Zhejiang and Fujian provinces all follow a log-normal distribution that can be used to make a rough estimate for the date of the last new confirmed cases in respective areas. In the version 2 continuation work, 9 additional days were added for the Chinese data to evaluate the previous predictions. The extra data then available from China follows the previous predicted trend supporting the usefulness of this simple technique. In the version 2 we also tested the feasibility for a non-specialist to make similar predictions using additional data from S Korea now available. In this third continuation the predictions for Version 2 are evaluated for S Korea and fits well the beginning of the decline but it seems to be difficult to bring down numbers of cases per day under about 100 new cases per day, potential reasons for this is discussed. To further evaluate when in a prediction becomes reliable the Chinese data was used to evaluate to make predictions for each day around the peak in number of cases and after2-3 consecutive days of decreasing new cases per day the prediction becomes reliable. In version 3 data for Italy just reaching this point was used to make further predictions for that country. A second new analysis was also added to use the fitted equation to detect when the acceleration of new cases per day stopped increasing exponentially. In the Chinese case this measured point coincides with the date of the complete Hubei lockdown and in the new Italian analysis it coincides with the mandatory Italian lockdown. Predicted dates for the end of the Italian outbreak is also added. In version 4 we expand the analysis to selected European countries, USA and the World as a whole and try to predict the end of the outbreak. We further discuss the apparent success of the used techniques that might work to introduce a “new normal” not very different to the previous to stop secondary outbreaks of COVID19 and future COVIDs that are sure to come.

Introduction: Variants of COVID-19 are responsible for 700 million infections and 7 million deaths worldwide. Vaccinations have high efficiency in preventing infection and secondary benefits of reducing COVID-19 hospital admissions, attenuating disease severity and duration of illness. Conflicting reports were published regarding COVID-19 among PLWH. Objective: The aim of this study was to evaluate COVID-19 morbidity, hospitalization and the magnitude of immunological response to sequential BNT 162b2 mRNA vaccines in PLWH regarding demographic and clinical factors. Results: Our retrospective study included 784 PLWH who had at least one anti- SARS-CoV-2 antibody test between March 2021 and October 2021. Half of our patients (392) had CD4 cells count above 500 cells/µl, 40.2% (315) had 200<CD4<500 cells/µL and only 9.8% (77) had CD4 <200 cells/µL at their last laboratory workup. The mean age was 50.2±12.2 years. About 90% of our patients were given at least two doses of the BNT 1626b2 Pfizer vaccines, about 60% received three doses of the vaccine. About a quarter of our patients (27.3%) had COVID-19 infection. Only 6 patients required hospital admission. All six patients recovered from COVID-19 infection. Titers of COVID-19 antibodies were lower for patients with CD4 cells count of less than 200 cells/ µL in the first, second and third serological tests with statistical significance. In a multinomial logistic regression the influence of other factors such as age, sex, previous COVID-19 infection on first COVID-19 antibodies titers was not significant. Conclusions: PLWH are responsive to COVID-19 vaccines. As was expected, patients with higher CD4 cells count have higher titers of COVID-19 antibodies and less severe illness. Age, sex and previous COVID-19 infection did not significantly affect antibodies titers according to our study. Larger prospective studies with control groups are needed to further characterize immunologic response to COVID-19 vaccination among PLWH.

Long COVID–19 syndrome is another vicious feature of COVID-19 infection, the mechanism remains unidentified. Several observational studies suggest that vaccinations might have protective and therapeutic effect on long COVID-19 and our study aimed to assess the influence of vaccination on COVID-19 patients. We performed an observational cohort study from October 2020 to July 2022, which included 503 patients (291 males and 212 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms (after 1 month of COVID-19 infection. The clinical and demographic data including vaccination status collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. More non-vaccinated patients acquired long COVID-19 than vaccinated. Patients with type 2 diabetes suffered from long COVID-19 in a smaller percentage than patients without diabetes. Gender, inhalational therapy due to chronic pulmonary disease and the number of complications have significantly influenced long COVID-19 development and the mostly vaccinated patients were older and with asthma/COPD. Our study confirmed that vaccination is a safe and effective measure to prevent the severe progression of acute disease and to lower the incidence of developing long COVID.

COVID-19 generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest Tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and the evaluation in the subsequent months showed an improvement in the evolutionary image, and with less than six months post-pathology, there was a commitment of 37 .7%, from six to twelve months, 20% and after 12 months, 9.9%. And as for most of the sample, 50.3% of the patients presented CT normalization in less than six months after infection, 23% normalized between six and twelve months, and 5.2% normalized the images after twelve months, with one remaining. Percentage of 17.3% who maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, in less than six months after the pathology, 59.3% of the patients already showed a regular exam; 12.3% normalized their function within six to twelve months, and 6.3% concluded a normal exam after twelve months of post-pathology evaluation. Only 3.6% of the patients still showed some alteration in this period.

In this case study, we describe a well-resourced private school system that implemented COVID-19 mitigation measures based on public health expert guidance as well as the lessons learned from this process. Avenues is a 10-year-old private school with campuses in NYC, São Paulo, Shenzhen, Silicon Valley, as well as online, which offers education at sixteen grades: 2 early learning years, followed by a pre-kindergarten–grade 12 school. We describe the mitigation measures Avenues implemented. We compare COVID-19 case prevalence at the school to the reported case prevalence in New York City, as reported by the New York State Department of Health. We compare the school's indoor air quality (IAQ) to ambient IAQ measures reported in the literature. The school's COVID-19 transmission mitigation measures successfully reduced the prevalence of COVID-19 among its students, staff, and faculty. The school also established a consistent high level of IAQ through various ventilation mechanisms. The school received positive parent and community feedback on the policies and procedures it established, with many parents commenting on the high level of communication and trust established by the school. This successful school reopening provides useful data for school closure and reopening standards to prepare for future pandemic and epidemic events.

The COVID-19 pandemics has had an unprecedented global impact, and the COVID-19 mass vaccination campaign has been commonly regarded as crucial to overcome the pandemics. Since all-cause mortality is the best way to measure the consequences of a health intervention, the present study was devised to analyze the all-cause mortality data of the United Kingdom (UK), which are made publicly available broken down by vaccination status. Data from April 2021 to May 2023 were retrospectively collected and analyzed according to age groups and vaccination status and the Standardized Mortality Ratio (SMR) for all-cause mortality and for non-COVID-19 were calculated in comparison to the corresponding unvaccinated groups. Results show that, since an age group dependent date, the all-cause mortality SMRs were increasing in any of the age groups considered. Initially, the all-causes death SMRs were less than 1 for all age groups, but due to their growth, for the age groups 18-39, 80-89 and 90+ years by a certain date they exceeded the reference value. For the other age groups, as long as the trend is maintained, it is possible to predict the date in which the SMR would reach the value 1. Non-COVID-19 SMR values show a very similar trend. Their initial values much lower than 1 suggest the presence of significant biases in the ONS dataset which lead to an underestimation of the risks for those vaccinated, as it is not plausible that the vaccine protects from causes other than COVID-19. The finding that all-cause mortality SMRs in vaccinated in comparison to unvaccinated people increases over time requires careful examination to understand the underlying factors. Meanwhile, the other major countries should undertake a systematic collection of all-causes mortality broken down by vaccination status, and should be implemented a moratorium of the promotion of mass vaccination campaigns.

Purpose: The healthcare pressure and emotional tension during the first year of the COVID 19 pandemic have been able to affect the health of healthcare personnel. Physical and psychological symptoms attributed to a work situation and or COVID 19 infection are describ ed in health professionals. Objective: to analyze the prevalence of physical and psychological symptoms directly or indirectly related to COVID 19 (occupational causes, illness or persistent COVID 19) after a 12 month pandemic. Methods: #COVID19PS is a cro ss sectional analytical study using an ad hoc questionnaire distributed through social media to record physical and psychological symptoms related to COVID 19 in health professionals. Variables: age, sex, geographical origin, profession, characteristics of the work environment, physical symptoms, Maslach test ( for health professionals. Univariate and bivariate statistical analysis using t distribution, Chi square, ANOVA using IBM SPSS v20®. Results: N=1.159 ( women, 21.8% men; 44.6% <35 years old, 23.9% between 35 45years); 96.5% Spaniards. Professions: 17.1% medicine, 12.7% nursing, 32% physiotherapy, 24.1% occupational therapy, 14.1% others; 47.5% belonged to direct care for COVID 19 patients. 28.2% had passed the disease and 3.7% had it acti ve. 61.6% had physical symptoms ( neurological, 31.7% musculoskeletal, 29.6% general, 20.9% gastrointestinal, 20.3% skin, 19.2% cardiovascular, 16% respiratory (p= 96.9% had a medium high Burnout index (p= 48.3% with high levels of Emot ional Exhaustion, 62.9% with medium high level of Depersonalization and 74% with medium low levels of Personal Accomplishment. Conclusion: all health professions present high rates of physical and burnout consequences of the first year of COVID 19 pandemic.

On 11th March 2020, the World Health Organization declared COVID-19 as a pandemic. Vaccination programs have advanced greatly in the global health period, despite widespread anti-vaccination attitudes and misinformation. Vaccine hesitancy of COVID-19 vaccine is currently a major issue in Saudi Arabia. This cross-sectional study was carried out from June 25, 2021 to October 2021 in order to investigate the knowledge levels of acceptance and hesitancy of COVID-19 vaccine among Saudi’s nationals. The data was collected through a close-ended structured questionnaire from a total of 565 respondents. Overall, 78.41% respondents were female, 62.48% having university level education and 61.06% were unemployed. Majority of the participants 82.30% (n=465) think that Pfizer vaccine has the highest efficiency against COVID-19. Our study concludes that majority of the participants have satisfactory knowledge about COVID-19 vaccination. Concerns over vaccine components, effectiveness of vaccine and possible side effects are among the key causes for vaccine hesitancy.

CoVID-19 is a multi-symptomatic disease which has made a global impact due to its ability to spread rapidly, and its relatively high mortality rate. Beyond the heroic efforts to develop vaccines, which we will not discuss, the response of scientists and clinicians to this complex problem has reflected the need to detect CoVID-19 rapidly, to diagnose patients likely to show adverse symptoms, and to treat severe and critical CoVID-19. Here we aim to encapsulate these varied and sometimes conflicting approaches and the resulting data in terms of chemistry and biology. In the process we highlight emerging concepts, and potential future applications that may arise out of this immense effort.

Objective: SARS-Cov-2 infection or COVID-19 is a global pandemic. From the time of identification to till, multiple clinical symptoms and parameters have been identified by the researchers of various countries and regions regarding the diagnosis and presentations of COVID-19 disease. In this manuscript, we investigated the primary symptoms and basic hematological presentations of SARS-CoV-2 infection among the Bangladeshi patients. Methodology: We have collected the disease history of mild to moderate degree of COVID-19 patients; hematological and biochemical on admission reports of moderate degree COVID-19 patients. All of them were tested positive for SARS-CoV-2 by RT-PCR in different institutes in Bangladesh. Results: According to this study though COVID-19 patients in Bangladesh commonly presented with fever, cough, fatigue, shortness of breath, and sore throat, but symptoms like myalgia, diarrhea, skin rash, headache, Abdominal pain/cramp, nausea, vomiting, restlessness, and a higher temperature of >100⁰F have a greater presentation rate and more frequent than other published studies. CRP and Prothrombin time was found to increase in all the patients. Serum ferritin, ESR, SGPT, and D-Dimer were found increased among 53.85%, 80.43, 44%, and 25% patients respectively. 17.39% of the patients had leukocytosis and neutrophilia. 28.26% of patients presented with lymphocytopenia. 62.52% of patients had mild erythrocytopenia. Conclusion: Despite some similarities, our study has evaluated a different expression in presenting symptoms in the case of COVID-19 patients in Bangladesh. CRP, Prothrombin time, serum ferritin, ESR, SGPT, D-Dimer, erythrocytopenia, and lymphocytopenia can be initial diagnostic hematological findings and assessment for prognosis COVID-19 disease. Also, gender variations have a different scenario of clinical and laboratory appearance in this region.

Background: COVID-19 pandemic has pulled us all a few steps back, were we never shake hands or hug each other when we meet our friends and family after a gap, but instead we greet them by saying Namaste and joining our hands together. As we all know, COVID-19 spreads through air and the only way to shield ourselves is by maintaining a safe distance from one another. Methodology: In order to conduct a meta-analysis on the number of COVID-19 cases in Kerala and India, the data was retrieved from various sites hosted by the government bodies. The data for analysis was collected from May 2020 to July 2020. The average number of days required to reach every 5000 fresh cases were also calculated using this data. COVID-19 has affected all the economy holistically regardless of financial, behavioral, or societal aspects. Conclusion: Lifting of the lockdown in a step by step process keeping in mind the necessities for the nation was a thoughtful act, but the people who mistook this opportunity and did not remain in quarantine after coming from abroad was recognized as the reasons behind the sudden and uncontrolled rise in the number of COVID-19 cases in Kerala, India. The government authorities had no other option but to lift the restrictions to reduce the economic burdens that had already affected the daily wage worker and farmers prompting them to give up their lives.

High rates of phosphorus (P) currently being applied to soils for the production of vegetables in the Mekong Delta, Vietnam has led to the concern of its negative effect on the economics and the environment. This research presents a comprehensive study on the determination of P supplying capacity in this region of Vietnam to examine the possibility of reducing P fertilizer input. One hundred twenty (120) soil samples were collected to evaluate total P and Bray 1 available P in the soils. Phosphorus maximum sorption, degree of P saturation, P release, and the effect of P fertilizer on corn (Zea mays L.) yield in greenhouse and fields were also determined. Total P concentrations of 56.7% soil samples evaluated yielded high P concentrations (>560 mg P/kg), while 74.2% of the samples had high Bray 1 available P concentrations (>20 mg P/kg soil). Maximum P sorption ranged from 149 to 555 mg P/kg soil, respectively and has negative correlation to available P (r = - 0.63*), degrees of P saturation ranged from 0.63 to 5.46% correlated to available P (r = 0.98**) and maximum P release ranged from 1.2 to 61.9 mg P/kg soil, respectively correlated to available P (r = 0.96**). Corn grown in soils with available P concentrations >15 mg P/kg did not respond to P fertilizer in greenhouse or field experiments. We conclude that many farmers in this region can reduce P fertilizer input, thus increasing their profits and reducing negative environmental impacts associated with excess soil P for sustainable agriculture.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

The aim of this study was to estimate the association between fear of COVID-19 and risk perception with preventive behavior in health professionals from three Latin American countries. An analytical cross-sectional study was conducted. Health professionals with on-site care in Colombia, Ecuador, Guatemala, and Peru were surveyed. Information was collected through an online self-report questionnaire. The main variables were preventive behavior as the dependent variable and fear of COVID-19 and risk perception as independent variables. Linear regression was used, and Beta coefficients and p-values were calculated. 435 health professionals were included, the majority were aged 42 years or older (45.29%, 95%CI: 40.65%-50.01%) and female (67.82%, 95%CI: 63.27%-72.05%). It was shown that the greater the fear of COVID-19, the greater the preventive behavior of COVID-19 infection (B=2.21, p=0.002 for total behavior; B=1.12, p=0.037 for additional protection at work; B=1.11, p<0.010 for hand washing). The risk perception of COVID-19 infection had a slight direct relationship with preventive behaviors (B=0.28, p=0.021 for total behavior; B=0.13, p=0.015 for hand washing), with the exception of the preventive behavior of using additional protection at work (p=0.339). We found that fear and risk perception are associated with increased practice of hand washing and use of additional protection at work. Further studies are required on the influence of working conditions, job performance and the occurrence of mental health problems in frontline personnel with regard to COVID-19.

Background: The uptake of COVID-19 booster vaccines has been significantly low. Therefore, it is questionable whether combining the COVID-19 booster vaccines with Influenza vaccines can increase the population's interest in taking such vaccines and manage the health pandemic effectively. Methodology: In this systematic review and meta-analysis, a synthesis of the findings and summary of a total of 30 research articles based on the topic, ‘combining influenza and COVID-19 booster vaccination strategy’ was undertaken. The research articles were identified from three databases, namely, PubMed, Cochran Library, and Google Scholar using specific keywords and inclusion criteria. However, research articles that were not peer-reviewed and not published in English were excluded from the systematic review and meta-analysis. The average risk ratio of the included articles was 0.78% based on a 95% CI. On the other hand, the heterogeneity between such studies was I² = 35%, while the statistical significance of their findings occurred at p < 0.05. The average p-value of the included research studies was p = 0.62, implying that the null hypothesis was not rejected in almost all the studies. Results: A synthesis of the chosen research articles revealed that when influenza and COVID-19 booster vaccines are combined, there is potential for an increase in the uptake of the latter, mainly because many populations have already been accustomed to taking influenza vaccines on an annual basis. Conclusions: In this way, through such findings, medical health experts can make informed decisions to increase the population's willingness to receive the COVID-19 booster vaccines.

Given the concerns of waning immunity from the primary COVID-19 vaccines and the first booster dose, we conducted an on-line cross-sectional study in May 2022 to investigate willingness to receive a second COVID-19 booster dose or a new COVID-19 vaccine and its associated factors. Overall, 22.7% of participants were willing to be vaccinated, 39.3% were unsure, but tend to be willing, 25.8% were unsure, 4.9% were unsure, but tend to be unwilling, and 7.4% were unwilling to be vaccinated. The main reasons against accepting a second COVID‐19 booster dose or a new COVID-19 vaccine COVID-19 dose included concerns about the side effects, the opinion that further vaccination is unnecessary, and effectiveness uncertainties. Males, younger individuals, participants without a previous COVID-19 diagnosis, and those with good/very good self-perceived physical health were significantly more frequently willing to receive a second COVID‐19 booster dose or a new COVID-19 vaccine. Also, increased fear of the COVID-19, increased trust in COVID-19 vaccination and decreased fear of a second booster dose or a new COVID-19 vaccine were associated with increased willingness. Our results show some hesitancy and unwillingness toward further COVID-19 vaccination and indicate that fear of COVID-19 and trust in COVID-19 vaccination affect public opinion

The world is currently, subjected to the worst health crisis documented in modern history; an epidemic led by the novel coronavirus disease 2019 (COVID-19). At the epicenter of this crisis, healthcare professionals continue working to safeguard our well-being. To the regular high levels of stress, COVID new heights even more to healthcare professionals so depending on the area, specialty, and type of work. Here we investigated what are the tendencies, or areas most affected. Through an adaptation of the original COVID-stress scale, we developed a remote, fast test designed for healthcare professionals of the Northeastern part of Mexico, an important part of the country with economic and cultural ties to the US. Our results showed 4 key correlations as highly dependent: Work area – Xenophobia (p &lt; 0.045), Work with COVID patients - Traumatic stress (p &lt; 0.001) and Total number of COVID patients per day – Traumatic stress (p &lt; 0.027), and Total number of COVID patients - Compulsive checking and reassurance. Overall concluding that normal levels of stress have increased (mild – moderate). Additionally, we further determine that the fear of being an asymptomatic patient (potential to spread without knowing) continues being a concern.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes, however more research is needed to strengthen the existing evidence basis as one of the most important limitation is the limited number of trials and the evaluation of varied therapies. The analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

Orthostatic hypotension (OH) is a condition marked by a significant drop in blood pressure upon standing, resulting from impaired autonomic regulation of vascular tone and blood volume. This study investigates the prevalence, physiological mechanisms, and occupational risk factors for OH among high-risk professions in Nepal, such as traffic police, security guards, and shopkeepers. Using a cross-sectional design, participants were evaluated for blood pressure variability, autonomic function, and fluid balance. The findings reveal a high incidence of OH, linked to reduced baroreceptor sensitivity and impaired sympathetic activation due to prolonged standing and inadequate hydration. This study highlights the need for tailored clinical interventions and workplace modifications to mitigate OH in vulnerable occupational groups.

Coronaviruse disease (COVID-19) outbreak has created an emergency globally, and social distancing and isolation is the only solution to prevent its spread. Several countries have announced fully locked on to tackle this pandemic. The recent COVID-2019 has shaken the globe with incidence cases of more than half-million cases, and a mortality toll of more than twenty thousand to date. The coronavirus family is inclusive of pathogen of both – animal species and humans, encapsulating the isolated severe acute respiratory syndrome coronavirus (SARS-CoV). Researchers round the globe have been dexterously working to decode this lethal virus. Many mathematical frameworks have also been depicted which have helped to understand the dynamics of the COVID-19. Research on coronaviruses continues to explore various aspects of viral replication and pathogenesis to understanding the predilection of these viruses to switch between species, to develop an infection in a new host, and to identify significant reservoirs of coronaviruses will dramatically aid in our potential to prophesize when and where potential epidemics may occur. Many of the non-structural and accessory proteins encoded by the viruses remain unclear and unknown. This systematic review highlights the current situation of the pandemic, virus genomic composition, pathogenesis, symptomatology, diagnosis, and prognosis along with mathematical models of disease transmission and dynamics.

Mortality due to suicide is amongst the largest public health concerns across the world today and in Bharat (India). There have been concerns that the COVID-19 pandemic has contributed to worsening mental health outcomes across the world, and in Bharat. Furthermore, long COVID has been proposed to be a major consequence of COVID-19, which can also worsen mental health outcomes. Therefore, our objective in this study was to analyse trends in suicide mortality across Bharat, and to compare these trends to changes prior to the COVID-19 pandemic; as well, we aimed to analyse if long COVID had any role in these changes. It was found that, at a national level, the average annual increase of the suicide rate between 2019 and 2022 was 0.7 per 100,000 people (6.41% increase)., There was also an average annual rise in suicide rates across 27 states/union territories (out of the 33 that were analysed). States/UTs with the highest annual increases since the start of the COVID-19, despite a decrease from 2018 to 2019, were Tamil Nadu (increase by 2.7; 15.17% increase), and Telangana (increase by 1.9; 9.22% increase), Multi-linear regression had shown that the annual suicide rate changes were not associated with COVID-19 deaths per 10,000 people (standardized beta coefficient = 0.077; p = 0.605) but were associated with COVID cases per 100 people (standardized beta coefficient = 0.578; p<0.001). It has been shown that suicide mortality has worsened, and long COVID may have a potential role in this in Bharat.

The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.

Background: COVID-19 is currently one of the most important medical challenges as it affects the entire population with children being infected as easily as adults. Objective: The study evaluated the mortality of under 17-year-olds and compare the frequency with that of adults in a cohort of 8986 COVID-19 positive patients hospitalized in a single care center. Design: retrospective clinical trial, all hospitalizations of COVID-19 positive patients as diagnosed by RT-qPCR were analyzed by revisiting their medical records. Setting: 8986 COVID-19 positive patients hospitalized in a Hospital de Base and the Infant and Maternal Hospital of São Jose do Rio Preto, SP, Brazil (HB/HCM) being these totals of 383 COVID-19 positive under 17-patients. Patients: patients COVID-19 positive under 17-year-olds were grouped by age and evaluated by analyzing their medical records. They were categorized as Group I, children, and adolescents under 19 years old and Group II, adults over 19 years. Results: Overall mortality in under 19-year-olds was 12 deaths, that is, 3.13% of the patients in this age group and 0.55% of the overall mortality from COVID-19. Mortality in the group of adults was 2197 equivalent to 24.45% of the hospitalized adults and 99.45% of overall deaths. Mortality was significantly higher for adults than for under 19-year olds (p-value < 0.0001). Regarding the different ages of children and adolescents, the number of deaths of under 1-year olds was 2/123 (1.62%), of 1-4 years it was 4/95 (2.11%), of 5-9 years it was 1/47 (2.13%), of 10-14 years it was 1/40 (2.5%) and of 15-19 years it was 4/78 (5.13%). There were no statistical differences between the different age groups ( p-value = 0.3). Conclusion: Mortality from COVID-19 in children and adolescents was lower than in adults and generally associated with other comorbidities with the main association being with heart disease.

Socio-demographic factors are responsible of health inequalities also in vaccination. The aim of this study was to evaluate their role at population level through a population-based study performed on the whole population entitled to receive COVID-19 vaccines in Umbria Region, Italy, and registered to the Regional Healthcare Service as of February 28th, 2021. Socio-demographic characteristics and vaccination status in terms of uptake at least one dose of any available vaccine, completion of the primary vaccination cycle and uptake of the booster doses as of February 28th, 2022 were col-lected from the Umbria regional database. The percentage of eligible population who did not initiate the COVID-19 vaccination, complete the full vaccination cycle and get the booster dose was 11.8%, 1.2% and 21.5% respectively. A younger age, being a not-Italian citizen, and not holding an ex-emption for chronic disease/disability and a GP/FP were associated to all the endpoints. Females, as compared to males, were more likely to not initiate the vaccination but less likely to not receive the booster dose. On the contrary, results on the deprivation index were not conclusive. The findings, beyond confirming current knowledge at population level, provide new inputs for better tailoring vaccination campaigns.